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The novel roles of RNA m6A modification in regulating the development infection and oxidative DNA damage repair of Phytophthora sojae

机译:RNA m6A 修饰在调控大豆疫霉发育、感染和氧化 DNA 损伤修复中的新作用

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摘要

N6-methyladenosine (m6A), a vital post-transcriptional regulator, is among the most prevalent RNA modifications in eukaryotes. Nevertheless, the biological functions of m6A in oomycetes remain poorly understood. Here, we showed that the PsMTA1 and PsMTA2 genes are orthologs of human METTL4, while the PsMET16 gene is an ortholog of human METTL16. These genes are implicated in m6A modification and play a critical role in the production of sporangia and oospores, the release of zoospores, and the virulence of Phytophthora sojae. In P. sojae, m6A modifications are predominantly enriched in the coding sequence and the 3’ untranslated region. Notably, the PsMTA1 knockout mutant exhibited reduced virulence, attributed to impaired tolerance to host defense-generated ROS stress. Mechanistically, PsMTA1-mediated m6A modification positively regulates the mRNA lifespan of DNA damage response (DDR) genes in reaction to plant ROS stress during infection. Consequently, the mRNA abundance of the DDR gene PsRCC1 was reduced in the single m6A site mutant ΔRCC1/RCC1A2961C, resulting in compromised DNA damage repair and reduced ROS adaptation-associated virulence in P. sojae. Overall, these results indicate that m6A-mediated RNA metabolism is associated with the development and pathogenicity of P. sojae, underscoring the roles of epigenetic markers in the adaptive flexibility of Phytophthora during infection.
机译:N6-甲基腺苷 (m6A) 是一种重要的转录后调节因子,是真核生物中最常见的 RNA 修饰之一。然而,m6A 在卵菌中的生物学功能仍然知之甚少。在这里,我们表明 PsMTA1 和 PsMTA2 基因是人 METTL4 的直系同源物,而 PsMET16 基因是人 METTL16 的直系同源物。这些基因与 m6A 修饰有关,并在孢子囊和卵孢子的产生、游动孢子的释放以及大豆疫霉的毒力中起关键作用。在 P. sojae 中,m6A 修饰主要富集在编码序列和 3' 非翻译区。值得注意的是,PsMTA1 敲除突变体表现出毒力降低,这归因于对宿主防御产生的 ROS 应激的耐受性受损。从机制上讲,PsMTA1 介导的 m6A 修饰在感染过程中对植物 ROS 胁迫的反应中正向调节 DNA 损伤反应 (DDR) 基因的 mRNA 寿命。因此,DDR 基因 PsRCC1 的 mRNA 丰度在单个 m6A 位点突变体 ΔRCC1/RCC1A2961C 中降低,导致 P. sojae 的 DNA 损伤修复受损并降低 ROS 适应相关毒力。总体而言,这些结果表明 m6A 介导的 RNA 代谢与大豆疫霉的发育和致病性有关,强调了表观遗传标记在疫霉菌感染期间适应性灵活性中的作用。

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